Acute Myeloid Leukemia With Recurrent Genetic Abnormalities Other Than Translocations

Session 2 of the workshop focused on cases of acute myeloid leukemia (AML) with gene mutations in the setting of a normal karyotype.

Among 22 AML cases submitted, 14 had the NPM1 mutation, most also accompanied by mutations of other genes such as FLT3-ITD, DNMT3A, or, rarely, TP53; three cases had the heterozygous CEBPA mutation; and two cases had MYC amplification.

We explored prognostic implications of gene mutations such as DNMT3A, issues related to the classification of AML cases with the NPM1 mutation, and myelodysplasia-related changes arising from chronic myelomonocytic leukemia after a short latency interval. Disparate patterns of treatment response to targeted therapy using an FLT3 inhibitor, designated as cytotoxic or differentiation, and their genetic underpinnings were described. Finally, a minimal screening panel for gene mutations and the optimal approach for monitoring minimal residual disease were discussed.

In aggregate, this session highlighted the need for a refined molecular classification of AML as well as improved risk stratification based on systematic assessment for genetic alterations and their evolution over time.